This application is for a Mentored Research Scientist Development Award (K01). The broad long-term objective of the proposed studies is to examine the role of neuroimmune interactions in peripheral mechanisms of sensory neuron plasticity. Outlined are the specific aims of this project. 1) Determine if changes in the response properties of surviving sensory neurons, mediated by altered levels of proinflammatory cytokines in the affected nerve, underlie the recovery of nociceptive thresholds after ablation of IB4-binding neurons (Vulchanova et al, 2001). These studies will employ immunohistochemistry, teased-fiber recording of single unit activity, behavioral analysis of anti-sense treatment, and proteomics-based differential expression analysis. 2) Determine if upregulation of proinflammatory cytokines in the injured nerve after Spinal Nerve Ligation (SNL) is associated with changes in intact sensory neurons that may underlie mechanisms involved in the development of neuropathic pain. This specific aim will be addressed using immuno-histochemistry, behavioral analysis of antisense treatment, and proteomics-based differential expression analysis. 3) Determine if inflammation-induced upregulation of cytokines in the intestinal wall is associated with altered response properties of visceral spinal sensory neurons. These studies will employ immunohistochemistry, teased-fiber recording of single-unit activity, and antisense treatment. These studies will elucidate the role of proinflammatory cytokines in states of sensory hypersensitivity and may lead to identifying new targets for chronic pain therapies. The project will allow the candidate to acquire expertise in proteomics and electrophysiology and will provide theoretical and experimental foundation for establishing independent research program in the underrepresented field of visceral pain.